The CA1 hippocampal serotonin level modulates anxiety-like behavior in neuropathic rats

Abstract

Clinical and experimental studies reported that anxiety is the neuropathic pain comorbidity but the mechanisms involved in this comorbidity incompletely cleared. The current study investigated the consequence of pain induced by peripheral neuropathy on the serotonin (5HT) level of the CA1 region of the hippocampus as a potential reason for anxiety associated with neuropathic pain. In this manner, 25 male rats inconstantly were subdivided between three experimental groups (control, sham, chronic constriction injury). Neuropathic pain initiated by the chronic constriction injury of the sciatic nerve (CCI) then, mechanical allodynia, hyperalgesia and anxiety-like behavior evaluated using the Von Frey filaments, radiant heat, open field test (OFT) and elevated plus maze(EPM) respectively. To investigate the probable mechanisms, the in vivo extracellular levels of serotonin assessed by microdialysis and reverse-phase high-pressure liquid chromatography (HPLC) in the CA1 region of hippocampus on days 14, 21 and 28 post-CCI. Our data suggested that CCI caused anxiety-like behavior in OFT and EPM test. Serotonin concentration in the CA1 region of the hippocampus significantly (P < 0.001, F=10) reduced in CCI rats when the pain threshold was minimum. Nevertheless, these alterations reversed while the pain threshold innate increased. Neuropathic pain initiated by constriction of the sciatic nerve induces anxiety-like behavior in rats. This effect applies through the decrease in serotonin concentration in the CA1 region of the hippocampus. When pain spontaneously alleviated serotonin level increased and anxiety-like behavior relieved.